Recombinant granulocyte colony stimulating factor (G-CSF) increases circulating neutrophil number and function. Administration of G-CSF improves host defense and decreases morbidity associated with infection in immunocompromised patients and animal models. It is unclear whether administration of G-CSF will have beneficial or harmful effects in immunocompetent patients at risk of or developing infection. We have shown that G-CSF pretreatment in a canine model of lethal bacterial peritonitis increases circulating neutrophil numbers, accelerates bacterial and endotoxin clearance and improves cardiovascular function and survival. In a subsequent set of studies we evaluated the effects of rG-CSF administered at the onset of bacterial sepsis rather than prophylactically. In these studies we found that rG-CSF, despite administration at very high dosages (40 to 80 ug/kg q12h), did not result in increased circulating neutrophil numbers and did not appear to offer a protective advantage. These findings suggested that sepsis associated events either directly inhibited the stimulatory effects of exogenous G- CSF, or alternatively resulted in a maximal inflammatory response by the host which was insensitive to the effects of exogenous G-CSF. In an additional set of studies, to determine whether sepsis decreases the bone marrow response to G-CSF, we are going to evaluate bone marrow neutrophil precursor number in animals challenged with bacteria and treated therapeutically with G-CSF.